Measurable Residual Disease in Decision-Making: An Opportunity, but Not a Promise

Health care providers, patients, and drug regulators have differing opinions on the use of measurable residual disease (MRD) to make decisions on treatment strategies for hematologic malignancies, according to speakers at a session of the 2025 European Hematology Association (EHA) Congress. They explained their perspectives and what they say is needed to take MRD use to the next level.

Session moderator Pierre Démolis, MD, PhD, of the European Medicines Agency (EMA), explained that the use of MRD as a barometer to make decisions—such as whether to change a therapeutic strategy or continue treatment—is relatively new, but it is perceived as an opportunity to make judgments on efficacy earlier than is possible with traditional end points such as overall survival (OS). But as the panelists’ experiences showed, the judgments that are drawn from MRD status and even the meanings of the terms involved can differ by one’s vantage point.

The perspectives shared during the session revealed that Europe may not be close to endorsing use of MRD to make regulatory decisions, as the US FDA’s Oncologic Drugs Advisory Committee did last year,1 but discussions are certainly active at all levels and stakeholders view MRD as a promising tool for getting treatments to patients sooner.

Stakeholders view MRD as a promising tool for getting treatments to patients sooner. | Image Credit: © Kirsten D:peopleimages.com - stock.adobe.com

How Patients Think of MRD

Anne-Pierre Pickaert, a patient advocate with Association Laurette Fugain and Support for Bone Marrow Transplant Recipients, explained that during her treatment for acute lymphocytic leukemia, MRD was described to her as the use of special tools to search for a tiny number of cells, and if her number was below a certain threshold, that would be a good sign—“an opportunity, but not a promise for long-term cure.” Patients know that MRD negativity is predictive of remission, she said, but just “because you haven’t found it, that it doesn’t mean it’s still not there and could be harmful to you.”

This awareness of the importance of MRD can provoke what Pickaert calls “MRD-xiety,” in which patients know that the results of the test can determine their access to the next line of treatment. From an advocacy perspective, many patient groups are demanding equal and timely access to MRD and then therapy. Approval decisions based solely on OS can take years and thus limit access to novel therapeutics, but Pickaert and her fellow advocates envision MRD as an early indicator that should be evaluated as a co–primary end point along with OS.

What Clinicians Need to See From MRD

Next, Nicola Gökbuget, MD, of the Frankfurt University Cancer Centre, delivered the clinician perspective. “If we consider MRD as an end point, we need clear terminology,” she said, and she explained how guidelines are being updated to clarify sensitivity, cutoffs, and definitions. She sees a valuable opportunity for MRD to be leveraged in clinical decision-making by identifying signs of relapse or treatment failure earlier than could be detected by traditional hematological markers such as platelet and neutrophil counts.2

“MRD is not only an end point; it’s an indication to treat with new compounds, and the reason is that the clinical situation deteriorates during the development of a full hematologic relapse,” Gökbuget said.

However, she provided several prerequisites for MRD-directed treatment, including historical data showing correlation between MRD response and outcome, standardized testing in reference laboratories, reimbursement of MRD testing, and clear MRD-based response criteria. These steps can be accomplished through joint efforts by academic study groups and industry, she added.

How Care Providers and Regulators Differ in Attitudes Toward MRD

After this input from a patient and a physician, the audience heard results from a survey of European health care professionals and regulators, which were presented by Anna Smit, MS, of Erasmus University Medical Center. This survey by the EMA in collaboration with EHA and the International Myeloma Society revealed that although most respondents were very familiar with MRD, the importance they ascribed to it in varying hypothetical scenarios differed by their role.

“Overall, health care professionals appeared to attribute more importance to MRD response, even if it meant accepting higher levels of toxicity, while the regulators attributed more importance to the toxicity and weighted the toxicity more heavily in certain scenarios,” Smit said.

Also, most providers agreed that MRD-negative status should be the preferred end point in clinical trials for newly diagnosed multiple myeloma, as well as that insistence on proof of progression-free survival benefits delays access to innovative treatments for patients with multiple myeloma. A majority of regulators disagreed with both of these statements.

However, both groups did agree that it’s essential to establish a globally consistent MRD testing approach that assures high sensitivity and accuracy globally, and both said it is very important to have short- and medium-term health-related quality of life data at the time of early decisions using MRD as an early end point.

The regulators’ hesitancy to adopt MRD could stem from a difference in definitions. Demolis explained that a “surrogate” measure has a very high bar to clear in the regulatory sense, and MRD does not yet meet that bar, but it can be used to contribute to a regulatory decision at an earlier time point, “provided that the final efficacy assessment will confirm at least no negative trend.”

In response to an audience question about the likelihood of international regulators working together to develop a more globally consistent approach to MRD, Demolis noted that cross-agency discussions take place every month “not just to come to a common opinion, but just to understand why the decisions could be different in the States vs in Europe.”

References

1. Caffrey M. After ODAC, what’s next for MRD testing in multiple myeloma? AJMC®. September 25, 2024. Accessed June 13, 2025. https://www.ajmc.com/view/after-odac-what-s-next-for-mrd-testing-in-multiple-myeloma-

2. Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131(14):1522-1531. doi:10.1182/blood-2017-08-798322